Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome

Bowers, Samuel J.; Vargas, Fernando; González, Antonio; He, Shannon; Jiang, Peng; Dorrestein, Pieter C.; Knight, Rob; Wright, Kenneth P.; Lowry, Christopher A.; Fleshner, Monika; Vitaterna, Martha Hotz; Turek, Fred W.

doi:10.1371/journal.pone.0229001

Cited by 65 publications

(53 citation statements)

References 89 publications

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“…In our study, the relative abundance of Firmicutes bacteria and the F:B ratio were lower in SF rats relative to controls at the same time when alpha diversity and butyrate-producing bacteria were also reduced. More severe models of SF (20 h/day) in a mouse model demonstrated an increase in the F:B after 5 days, but this study did not have an intermediate measure to determine if there was an initial decline in the F:B ratio similar to our study ( 13 ). Many putative SCFA-producing bacteria belong within the phylum Firmicutes, providing a possible explanation for the simultaneous rise in SCFA-producing bacteria and the relative abundance of Firmicutes bacteria at late SF ( days 20 and 27 ).…”

Section: Discussioncontrasting

confidence: 45%

Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats

Maki

Burke

Calik

et al. 2020

Physiological Genomics

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The gut microbiota, via the production of metabolites entering the circulation, plays a role in blood pressure regulation. Blood pressure is also affected by the characteristics of sleep. To date, no studies have examined relationships among the gut microbiota/metabolites, blood pressure, and sleep. We hypothesized that fragmented sleep is associated with elevated mean arterial pressure, an altered and dysbiotic gut microbial community, and changes in fecal metabolites. In our model system, rats were randomized to 8 h of sleep fragmentation during the rest phase (light phase) or were undisturbed (controls) for 28 consecutive days. Rats underwent sleep and blood pressure recordings, and fecal samples were analyzed during: baseline ( days −4 to −1), early sleep fragmentation ( days 0–3), midsleep fragmentation ( days 6–13), late sleep fragmentation ( days 20–27), and recovery/rest ( days 28–34). Less sleep per hour during the sleep fragmentation period was associated with increased mean arterial pressure. Analyses of gut microbial communities and metabolites revealed that putative short chain fatty acid-producing bacteria were differentially abundant between control and intervention animals during mid-/late sleep fragmentation and recovery. Midsleep fragmentation was also characterized by lower alpha diversity, lower Firmicutes:Bacteroidetes ratio, and higher Proteobacteria in intervention rats. Elevated putative succinate-producing bacteria and acetate-producing bacteria were associated with lower and higher mean arterial pressure, respectively, and untargeted metabolomics analysis demonstrates that certain fecal metabolites are significantly correlated with blood pressure. These data reveal associations between sleep fragmentation, mean arterial pressure, and the gut microbiome/fecal metabolome and provide insight to links between disrupted sleep and cardiovascular pathology.

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Section: Discussioncontrasting

confidence: 45%

Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats

Maki

Burke

Calik

et al. 2020

Physiological Genomics

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“…Collectively, these studies and others [ 25 , 40 ] highlight a contributory role of perturbations to microbiota-gut-brain axis signalling in the manifestation of OSA-induced cardiorespiratory dysfunction. There is a growing interest in developing strategies to manipulate the microbiota as a potential therapeutic intervention in the treatment of cardiorespiratory disease.…”

Section: Introductionmentioning

confidence: 67%

Prebiotic administration modulates gut microbiota and faecal short-chain fatty acid concentrations but does not prevent chronic intermittent hypoxia-induced apnoea and hypertension in adult rats

et al. 2020

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Background Evidence is accruing to suggest that microbiota-gut-brain signalling plays a regulatory role in cardiorespiratory physiology. Chronic intermittent hypoxia (CIH), modelling human sleep apnoea, affects gut microbiota composition and elicits cardiorespiratory morbidity. We investigated if treatment with prebiotics ameliorates cardiorespiratory dysfunction in CIH-exposed rats. Methods Adult male rats were exposed to CIH (96 cycles/day, 6.0% O 2 at nadir) for 14 consecutive days with and without prebiotic supplementation (fructo- and galacto-oligosaccharides) beginning two weeks prior to gas exposures. Findings CIH increased apnoea index and caused hypertension. CIH exposure had modest effects on the gut microbiota, decreasing the relative abundance of Lactobacilli species, but had no effect on microbial functional characteristics. Faecal short-chain fatty acid (SCFA) concentrations, plasma and brainstem pro-inflammatory cytokine concentrations and brainstem neurochemistry were unaffected by exposure to CIH. Prebiotic administration modulated gut microbiota composition and diversity, altering gut-metabolic (GMMs) and gut-brain (GBMs) modules and increased faecal acetic and propionic acid concentrations, but did not prevent adverse CIH-induced cardiorespiratory phenotypes. Interpretation CIH-induced cardiorespiratory dysfunction is not dependant upon changes in microbial functional characteristics and decreased faecal SCFA concentrations. Prebiotic-related modulation of microbial function and resultant increases in faecal SCFAs were not sufficient to prevent CIH-induced apnoea and hypertension in our model. Our results do not exclude the potential for microbiota-gut-brain axis involvement in OSA-related cardiorespiratory morbidity, but they demonstrate that in a relatively mild model of CIH, sufficient to evoke classic cardiorespiratory dysfunction, such changes are not obligatory for the development of morbidity, but may become relevant in the elaboration and maintenance of cardiorespiratory morbidity with progressive disease. Funding Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland. APC Microbiome Ireland is funded by Science Foundation Ireland, through the Government's National Development Plan.

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“…Several fecal metabolites correlated with blood pressure, which might provide an insight into the reported link of sleep fragmentation and deleterious cardiovascular changes [ 86 ]. Furthermore, the effects of sleep fragmentation on the fecal metabolome and microbiome were investigated in mice [ 83 ]. A sub-chronic, five-day sleep disruption protocol caused a change in the level of bacterially-modified metabolites, such as bile acids, and caused a reduction of beneficial bacterial genera.…”

Section: Sleep Fragmentationmentioning

confidence: 99%

Metabolomics in Sleep, Insomnia and Sleep Apnea

Humer

Pieh

Brandmayr

2020

IJMS

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Sleep-wake disorders are highly prevalent disorders, which can lead to negative effects on cognitive, emotional and interpersonal functioning, and can cause maladaptive metabolic changes. Recent studies support the notion that metabolic processes correlate with sleep. The study of metabolite biomarkers (metabolomics) in a large-scale manner offers unique opportunities to provide insights into the pathology of diseases by revealing alterations in metabolic pathways. This review aims to summarize the status of metabolomic analyses-based knowledge on sleep disorders and to present knowledge in understanding the metabolic role of sleep in psychiatric disorders. Overall, findings suggest that sleep-wake disorders lead to pronounced alterations in specific metabolic pathways, which might contribute to the association of sleep disorders with other psychiatric disorders and medical conditions. These alterations are mainly related to changes in the metabolism of branched-chain amino acids, as well as glucose and lipid metabolism. In insomnia, alterations in branched-chain amino acid and glucose metabolism were shown among studies. In obstructive sleep apnea, biomarkers related to lipid metabolism seem to be of special importance. Future studies are needed to examine severity, subtypes and treatment of sleep-wake disorders in the context of metabolite levels.

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Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome

Cited by 65 publications

References 89 publications

Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats

Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats

Prebiotic administration modulates gut microbiota and faecal short-chain fatty acid concentrations but does not prevent chronic intermittent hypoxia-induced apnoea and hypertension in adult rats

Metabolomics in Sleep, Insomnia and Sleep Apnea

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